THE PATIENT’S GUIDE ●
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TO
M EDICAL T ESTS
THE PATIENT’S GUIDE ●
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TO
M EDICAL T ESTS ● ●
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Everything You ...
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THE PATIENT’S GUIDE ●
●
TO
M EDICAL T ESTS
THE PATIENT’S GUIDE ●
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TO
M EDICAL T ESTS ● ●
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Everything You Need to Know About the Tests Your Doctor Orders ●
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Joseph C. Segen, M.D., F.C.A.P., F.A.S.C.P. and
Josie Wade, R.N., J.D.
The Patient’s Guide to Medical Tests, Second Edition Copyright © 2002 Joseph C. Segen, M.D. All rights reserved. No part of this book may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information, storage, or retrieval systems without permission in writing from the publisher. For information contact: Facts On File, Inc. 132 West 31st Street New York NY 10001 Library of Congress Cataloging-in-Publication Data Segen, J. C. The patient’s guide to medical tests : everything you need to know about the tests your doctor orders / Joseph C. Segen and Josie Wade —2nd ed. p. cm. Includes index. ISBN 0-8160-4651-4 1. Diagnosis—Popular works. 2. Diagnosis, Laboratory—Popular works. I. Wade, Josie. II. Title. RC71.3.S424 2002 616.07'5—dc21 2002018824 Facts On File books are available at special discounts when purchased in bulk quantities for businesses, associations, institutions, or sales promotions. Please call our Special Sales Department in New York at (212) 967-8800 or (800) 322-8755. You can find Facts On File on the World Wide Web at http://www.factsonfile.com Cover design by Cathy Rincon Text design by Nancy J. Hajeski Printed in the United States of America MP FOF 10 9 8 7 6 5 4 3 2 1 This book is printed on acid-free paper
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TABLE
OF
CONTENTS
Introduction . . . . . . . . . . . . . . . . . . . . . . vii Alphabetical Listings . . . . . . . . . . . . . . . . . 1 Glossar y . . . . . . . . . . . . . . . . . . . . . . . . .339 Medical Abbreviations and Symbols . . . . . .394 Index . . . . . . . . . . . . . . . . . . . . . . . . . . .397
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J.W.: To my sons, Caleb and Mackenzie, who give my life joy, purpose, and direction. And in loving memory of my hero, my mentor, my daddy, Curtis E. Wade (6.24.30–4.5.02) J.C.S.: To David, my purpose; to Nikki, my hopes; to Joseph, my dreams; to Tish, my passion ❖ In loving memory of: Lewis Anthony (Tony) Sutin (11.11.59–1.16.02), Dean, Appalachian School of Law, Grundy, Virginia Taken too soon and sorely missed
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INTRODUCTION
M
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ost patient management–related questions asked by physicians can be answered by well-established and routine laboratory tests, radiologic and imaging studies, and various forms of endoscopy, including colonoscopy. These “garden-variety” tests and studies are widely used to screen for the possible presence of a particular condition, diagnose a specific disease, or monitor a finding in a person known to have and undergoing treatment for a particular disorder. Garden-variety tests consume the bulk of money spent on the diagnostic end of health care. Diagnostic medicine is constantly evolving. Advances in technology have had a broad impact on medical testing, both in terms of speed with which results are available and the types of answers that can be obtained from ever smaller specimens, new imaging modalities, and the emerging field of molecular medicine. These same advances have led to significant improvements in the process of testing, too, from the point of obtaining a specimen to providing the results to the physician. Specimen processing, specimen throughput, safety for the workers handling the specimens, and the reliability of results have all benefited from technological advances. Likewise, automated chemistry and hematology instruments can now provide thousands of results per hour, and microbiology analyzers can identify bacteria and determine which antibiotics will be useful in managing specific infections within a few hours. A common source of error in diagnostic testing is the mixing of specimens, which is now minimized with bar code readers and sample identification procedures that are implemented from the moment the specimen is obtained. Larger laboratories increasingly use robotics to handle specimens, further reducing human error. Many new tests have been developed in molecular medicine, oncology, virology, cardiology, and other fields that fine-tune the diagnosis and monitoring of more common disorders. These tests are becoming part of the routine diagnostic armamentarium. In addition, magnetic resonance imaging
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Introduction
(MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET) procedures are now replacing traditional radiologic (X-ray) studies in many areas, because they take “pictures” of various parts of the body without exposing patients to radiation. Interpretation of images has been made easier by the use of contrast media and image enhancers.
– THE PURPOSE
OF A
TEST –
For the sake of simplicity, all medical testing can be lumped into several categories: 1. Screening tests, which detect an abnormality typically found in a par ticular condition requiring therapy. Screening tests include measurement of urine glucose to detect diabetes mellitus, prostate-specific antigen to identify prostate cancer, blood pressure to detect hypertension, and fecal occult blood to detect colon cancer. 2. Diagnostic tests, which are used in clinical medicine to determine if a patient’s chief complaint (medical jargon for the reason that the patient went to his or her doctor) indicates the presence of a particular condition requiring therapy. Diagnostic tests include an electrocardiogram (EKG) to detect a heart attack; colonic biopsy to diagnose cancer, and TSH to diagnose thyroid disease. 3. Monitoring tests, which are used to “follow” a person with a particular disease to determine whether the patient is compliant (following the prescribed treatment plan) or whether the disease, such as cancer, is in remission or has reappeared. Monitoring tests include serial measurement of CEA (carcinoembryonic antigen) which rises in patients whose colon cancer reappears after therapy; hemoglobin A1c to determine how well controlled the blood sugar levels are in a person with known diabetes mellitus; and cholesterol levels to determine whether a drug being used to lower a patient’s cholesterol levels are sufficiently effective. 4. Forensic tests, which provide results that may be used in a civil court (for example, for paternity testing, or a criminal court (for example, DNA analysis of blood stains), possibly to link a person to criminal activity. This last category of testing is outside of the scope of this book
– SPECIMEN COLLECTION – Venous blood usually reflects the body’s physiologic state and is easily obtained by venipuncture, a relatively safe procedure when obtained by a trained phlebotomist. A small needle is inserted into a vein in the arm, and blood is drawn into a vacuum tube. The major risk of this procedure is hematoma at the site used for drawing the sample. Sterile, disposable equipment is used. The danger of infection to the patient is almost nonexistent. Blood specimens are also obtained from arteries in the thigh when blood gases are ordered. This is generally done in a hospital setting by specialized
Introduction
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phlebotomy teams. Capillary blood is required for some microtechniques commonly used in children. This is generally done by a phlebotomist pricking a fingertip and drawing blood drops into a small (capillary) tube. Serum is obtained from whole blood by allowing the blood to clot after it is drawn into a specimen container. The resulting clot is centrifuged, and the liquid remaining in the top of the tube is serum. Serum is the specimen most commonly used for chemistry tests. Plasma is obtained from whole blood to which anticoagulants have been added. The type of anticoagulant depends on the test requested. The anticoagulated whole blood is centrifuged, and the liquid remaining in the top of the tube is plasma. It is slightly different in composition from serum and cannot always be used as a substitute. Pleural fluid is present in the lining of the lungs, is increased in various disease states, and can be obtained by a procedure called thoracentesis. A needle is inserted into the pleural lining, and fluid is withdrawn. This is generally a hospital-based procedure and carries some risk of pneumothorax (perforation of the lung). There are several chemistry tests run on pleural fluid, but analysis for unusual cells, bacteria, and viruses are the tests most commonly performed on this fluid. Synovial or joint fluid is obtained by inserting a needle into the joint and withdrawing fluid via a syringe. It is usually taken from a swollen or painful large joint, often the knee, to determine the cause of the swelling. Cerebrospinal fluid bathes the spinal cord and covers the brain. It is obtained by inserting a needle into the spinal canal and withdrawing fluid via a syringe, a procedure carried out by a physician. This fluid is usually analyzed when neurologic symptoms occur. Urine specimens are classified as random or 24 hour: Random urine specimens can be obtained at any time by voiding into a clean, dry specimen container. Urine collected over a 24-hour period provides the best specimen for analysis. The first morning’s specimen is discarded. All urine voided during the next 24 hours, including the following morning’s specimen, is collected in the container provided by the laboratory. For some tests, a special preservative, usually a weak acid or base, is placed in the collection container by the laboratory. Because some of the preservatives are hazardous, special care must be taken when handling these containers.
– WHAT AFFECTS
THE
RESULTS –
Test results can be changed by various factors, for example, the way in which the specimen was obtained and subsequently handled by laboratory personnel. A traumatic phlebotomy, one that causes a hematoma, can affect tests in several ways. The most common form is seen in hemolysis, a situation in which red blood cells burst and release their contents into the serum. Many tests are adversely affected by hemolysis, and the results are difficult to interpret. Some tests require that the serum or plasma be frozen in order to ensure the stability of the substance being analyzed, especially if the specimen is shipped to a reference laboratory. Failure to freeze the specimen or thawing the specimen in transit will cause false negative results. Other tests
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Introduction
require that the specimen be kept at room temperature, as freezing or chilling causes deterioration of the substances being tested. Blood, plasma, and serum specimens are drawn into tubes containing various additives. The color of the tube’s stopper has been standardized and indicates the additive(s) in the tube. Many tests require that the patient follow a prescribed diet or even fast overnight before testing. If these restrictions are not observed, test results can be invalid. This is especially true if the patient does not inform the laboratory of failure to follow the prescribed restrictions and the tests are performed as usual. Various prescription and nonprescription drugs, including aspirin, laxatives, cold pills, cough preparations, sleeping aids, vitamins, nose drops, pain relievers, and stomach antacids can markedly alter test values. The American Association of Clinical Chemists maintains a list of nearly 10,000 specific drug-related changes on laboratory results. Daily routines, including eating and sleeping habits, may alter the results of certain tests, especially hormone levels in the blood. Test results may differ depending on whether a patient was lying down or standing up just before blood is taken. Excessive exercise, such as long-distance running, can produce abnormal values even in the absence of disease. A person’s sex, age, height, weight, and body surface area must be considered when interpreting the results of a medical test. Many tests have different reference ranges depending on these factors.
– WHERE TESTS ARE PERFORMED – Clinical laboratory tests are performed in hospitals or commercial laboratories. Testing is closely monitored so that only necessary testing is performed. In order to reduce costs, hospital laboratories generally perform the most routine tests, while less-common tests are sent to commercial laboratories. Generally, the larger the hospital, the larger the testing menu. Most physicians, clinics, and hospitals contract with commercial laboratories for testing and ancillary services that are not provided by their primary hospital laboratory. Radiologic tests and images are obtained either in a hospital or in a freestanding, for-profit imaging center, where the tests usually cost more than they do in the hospital Endoscopic procedures, in particular of the gastrointestinal tract can be performed either in a hospital or a physician’s office. Certain endoscopies carry an increased risk of complications and thus are more prudently performed in a hospital, where the complications can be better managed than they could be on an outpatient basis.
– COSTS – Most patients do not pay directly for medical testing but rather indirectly through health insurance plans. Usually people do not question the necessity for medical tests because they rarely see a bill, and as a result, everyone pays
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for unnecessary testing through higher premiums. It is, therefore, extremely important to review the invoices that insurance carriers submit. The price of medical tests reflects the cost of equipment and labor. Routine high-volume chemistry analyzers cost up to $400,000. In certain settings, such as commercial labs, multiple instruments of this kind may be needed to keep the operation functioning “24-7.” Specialized analytical instruments can cost up to $1 million. Labor is another expense incorporated into the price of a particular test. Few consumers of laboratory tests realize how many people (five to eight, depending on the lab) are involved in handling each specimen from the time it is obtained until the result is available. Also behind the scenes are people involved in billing, client services, and warehousing. Hospitals and commercial laboratories have become extremely efficient in providing testing services and have been able to keep costs low. Despite cost-containment efforts, the price tag for medical testing in the United States alone is estimated to exceed $100 billion per year.
– HOW
TO
USE THIS BOOK –
The tests in this book are listed in alphabetical order under the name most commonly used by physicians. Because of the large number of tests available, not all tests are listed in this book. We have attempted to list the tests most commonly used by physicians and have surveyed hospitals, commercial labs, and physicians to determine which tests should be included. If there is a particular test not listed in this book, the laboratory or medical facility that performs it will provide you with appropriate literature explaining the test and what procedures should be followed. Under each listing there is a description of the test, what is required for performing the test, the reference range, what abnormal values may signify, and the cost of the test. Any precautions in the evaluation of results and risks to the patient are noted under the comments section. For some tests a full entry (patient preparation, procedure, specimen, reference range, abnormal values, and cost) is not relevant because the test may be new, performed only in major medical centers, or performed only under special circumstances. Some tests are discussed briefly in the glossary. Following is a description of the test entry format: Description: This includes a general description of what the test measures. Patient preparation: Any instructions for the patient or special procedures involved in performing the test are listed here. Procedure: The specimen type and particular procedures involved in procuring the specimen are described here. Reference range: This is the range of values observed for persons free of disease. A value outside of this range does not necessarily mean a disease process is involved. Other test results and physical findings must be evaluated in order to reach a definitive diagnosis. Abnormal values: The diseases or symptoms that may be associated with abnormal results are listed here. In most cases the ordering physician is using the test to aid in determining the most likely cause of the symptoms.
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Introduction
Cost: The cost of the test is listed as a range. Testing costs vary widely depending on the type and location of the facility performing the test. Comments: Any special instructions or precautions are given in this section. A consumer of medical care needs a basic understanding of various diagnostic procedures in order to make intelligent choices. This book provides information that the reader, as a consumer of health care, needs to evaluate options when seeking such care.
– WHAT’S NEW
TO THE
SECOND EDITION –
Medical science continues to make advancements on many fronts at the same time. Although diseases don’t change, understanding of them does. With that understanding comes the ability to diagnose medical conditions at earlier stages with fewer false positive results, ultimately improving the quality of care provided at the bedside. In 1997, when the first edition was published, a number of first-generation tests were available. As an example, serum troponin I, an exquisitely sensitive marker for damage to heart muscle, was available for clinical use; unfortunately, the first-generation test proved to be clinically unreliable. That unreliability translated into needless cardiac catheterizations to confirm coronary arterial blockage that simply did not exist. The first-generation troponin assay therefore was an example of a test being too sensitive (in this case, the test detects an abnormality, damage to heart muscle), but not specific enough (not all heart muscle damage is due to ischemia or blockage in blood flow but rather other causes, such as myocarditis or inflammation of heart muscle). The second edition of The Patient’s Guide to Medical Tests includes nextgeneration tests, such as the new troponin assay, and new tests for old diseases, such as HER-2 for breast cancer. Obsolete tests, such as the Kveim test and LE cell test, have been passed to the glossary and will eventually be swept into the dustbin. New to the second edition is a brief discussion of common medical conditions and cancers and tests used to diagnose them. Test prices have been updated. The atrocities of September 11, 2001, changed virtually every aspect of modern life. Shortly after the World Trade Center and Pentagon attacks, a number of cases of anthrax were reported, raising the scepter of bioterrorism as a vehicle for extremists to advance their particular agenda. In this second edition, multiple entries are dedicated to those infections and causative agents that have the greatest potential for use as biological weapons. Because few physicians have first-hand experience with these diseases, we are grateful for the extensive material provided by the Centers for Disease Control and Prevention in Atlanta, Georgia; the U.S. Army Medical Research Institute of Infectious Diseases at Fort Detrick, Maryland; and other contributing agencies. This present edition has been markedly enhanced by my coauthor, Ms. Josie Wade, whose 14 years of clinical experience in intensive and emergency
Introduction
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xiii
patient care is coupled with a lawyer’s perspective on liability and risk management. We are both grateful to Suzy Matney and Cassie Davis for the thankless grunt work in updating prices on the procedures described in this work.
●
A
●
abdominal tap (abdominal drainage, belly tap, paracentesis, peritoneal fluid analysis) An invasive procedure in which a very long needle is inserted in the abdominal cavity to obtain fluid for either diagnostic or therapeutic purposes. The abdominal tap is a rapid way for clinicians in a hospital setting to distinguish a “surgical” abdomen (i.e., one requiring surgery) from a “nonsurgical” abdomen. Diagnostic paracentesis is performed to determine the cause of an increase in intraabdominal fluids. This is most commonly due to cirrhosis of the liver but is also caused by carcinoma, inflammation (peritonitis, pancreatitis, ruptured diverticulitis), and abdominal trauma with rupture of organs or blood vessels. One of the more important laboratory values obtained in the analysis of peritoneal fluid is the protein level, which is low in transudates (e.g., ascitic fluid) and high in exudates (e.g., inflammation and malignancy). The abdominal tap provides useful information in about 80% of cases; it may reveal unclotted blood, which indicates that bleeding is occurring within the abdomen; inflammatory cells, which suggests pancreatitis, appendicitis, diverticulitis, or rupture of an organ; or malignant cells, which may be the first indication of cancer. Patient preparation Before the procedure, patients may be given a tranquilizer. Procedure The patient lies on his or her back, and the abdomen is sterilized with appropriate cleansing solutions. The procedure consists of the insertion of a long, 20- or 18-gauge needle on either side of the navel, from which the physician obtains fluids for chemical analysis and a sample of cells to be examined under the microscope. Specimen Peritoneal fluid. Reference range Normally a few mesothelial cells may be seen in the fluid obtained from an abdominal tap. Abnormal values Fresh blood and inflammatory or malignant cells may be seen as indicated above. Cost $100–$225. ACE See angiotensin-converting enzyme. 1
2
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acetaminophen
acetaminophen (Tylenol) A drug used to relieve pain and reduce fever that, if taken in excess, can result in fatal liver failure, and serum levels of acetaminophen are usually requested by the patient’s physician when an overdose is suspected. Patient preparation No preparation is required, other than for drawing blood. Procedure Acetaminophen is measured by immunoassay procedures, using either fluorescence polarization immunoassay (FPIA) or ELISA. Specimen Serum, plasma, urine. Reference rang Up to 25 µg/ml is within the normal therapeutic range. Abnormal values Toxicity occurs at levels of greater than 50 µg/ml. Cost $60–$110. acetone See urinalysis. acetowhite lesion A whitish patch on a woman’s cervix that is seen by colposcopy when “painted” with Lugol solution (5% acetic acid, vinegar). The white often indicates changes on the surface of the cervix that pathologists call hyperkeratosis and parakeratosis. These changes may be associated with cancer, precancerous changes known as cervical intraepithelial neoplasia (CIN, also called dysplasia), and infection by the human papillomavirus (HPV), which causes condyloma, a precancerous change. Patient preparation The preparation is that for a colposcopy. Procedure The woman lies on her back with her feet in stirrups while the gynecologist examines the cervix with a low-power microscope. The gynecologist coats the cervix with Lugol solution, which stains normal tissue a mahogany brown color, leaving areas of potential disease (e.g., HPV infection, squamous metaplasia, dysplasia, and carcinoma) unstained. Whitish areas that suggest an abnormal lesion are biopsied, and the biopsy is submitted to a pathologist for evaluation. Specimen Tissue sample (i.e., a biopsy). Reference range No lesion, or mild inflammation. Abnormal values HPV infection, metaplasia, dysplasia, and carcinoma. Cost See cervical intraepithelial neoplasia, colposcopy, HPV. acetylcholine receptor antibodies A family of antibodies that develops in myasthenia gravis, a disease that affects the transmission of nerve impulses. In normal muscle, the chemical acetylcholine is released from nerve endings and binds to the molecules known as receptors, resulting in muscle contraction. In myasthenia gravis, antibodies act against the patient’s own acetylcholine receptors. This occurs in up to 95% of patients with myasthenia gravis and prevents the binding of acetylcholine to the receptors, causing muscle weakness. Patient preparation No preparation is required, other than for drawing blood. Procedure The antibodies are measured in the serum by RIA.
acid-fast stain
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3
Specimen Serum. Specimen must be kept at room temperature until analysis. Reference range Negative, or less than 0.03 nmol/L. Abnormal values Acetylcholine antibodies are found in myasthenia gravis. Cost $75–$175. Comments Failure to maintain the specimen at room temperature will inter-
fere with results. Patients undergoing thymectomy, thoracic duct drainage, immunosuppressive therapy, or plasmapheresis may show reduced levels. Patients with amyotrophic lateral sclerosis may show false-positive results. acetylcholinesterase See cholinesterase. acetylsalicylic acid
See aspirin.
acid-fast stain Acid-fast stain is a general term for any number of special stains used to identify Mycobacterium species, the most important of which is M. tuberculosis, the bacterium that causes tuberculosis. Acid-fastness is related to the composition of the bacterium’s outer capsule. While acid-fastness is relatively specific for mycobacteria, it is also seen in some pollens, keratohyaline (a skin protein), lipofuscin (a product of cellular degradation), lead inclusions, and other microorganisms, including Nocardia, Histoplasma, and other bacteria. There are other, nontuberculous mycobacteria in the environment that stain with the acid-fast technique. In the appropriate setting, however, a positive acid-fast stain is usually regarded as evidence that the person has tuberculosis. Pulmonary tuberculosis is the most serious of the conditions caused by M. tuberculosis, which can be diagnosed either on a smear of sputum or on a biopsy of lesions of the lungs that are “suspicious” when the upper respiratory tract is examined by bronchoscopy. Other body sites can be evaluated by aspiration of fluids or by tissue biopsy. Patient preparation Brush teeth or remove dentures and rinse mouth with water before obtaining a “deep cough” specimen. Saliva from the mouth is of little use. Tuberculosis from other body sites can be evaluated by aspirating fluids or by biopsy of tissues using standard aseptic procedures with local anesthesia. Procedure Once the specimen is obtained from the patient, it is smeared on a glass slide that is dipped in a number of dyes to determine whether the organism is acid-fast or not. M. tuberculosis is slow to grow in culture; identification and determination of sensitivity to antibiotics may take four to six weeks. Specimen Sputum. Reference range No acid-fast staining. Abnormal values Positive staining for acid-fast bacteria indicates the presence of Mycobacterium species. This finding must be followed up by a culture to determine the species and its sensitivity to antibiotics. A negative result must also be followed up by a culture since this test is of relatively low sensitivity. Cost $50–$100.
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acidified serum lysis test
Comments With the recent increase in tuberculosis and the prevalence of immunosuppressed individuals, particularly those with AIDS, newer techniques have been developed to speed the detection and identification of mycobacteria. The technique of polymerase chain reaction (PCR) may be used to detect early growth of M. tuberculosis. PCR shortens the time needed to identify mycobacteria to 24 hours, allowing early administration of antibiotics. A recent phenomenon of considerable concern to public health authorities is the emergence of mycobacteria that are resistant to the antibiotics formerly successful in treating tuberculosis.
acidified serum lysis test
See Ham test.
acid infusion test See Bernstein test. acid mucopolysaccharides This test is used in the diagnosis of mucopolysaccharidosis, a genetic defect of carbohydrate metabolism. An enzyme deficiency causes dermatan sulfate and heparin sulfate to accumulate in tissues. Its most severe form is Hurler’s syndrome, also known as gargoylism, which has an early onset and commonly causes death by the age of 10. Patient preparation No preparation is required. Procedure This test is performed on a refrigerated 24-hour urine specimen which is sent to the laboratory immediately after collection. See timed collection in Glossary. Specimen Urine. Reference range The normal values vary with age and are expressed as milligrams of glucuronic acid per gram of creatinine per 24 hours. At age two, this value is from 8 to 30, by early adolescence, it drops to between 0 and 12. Abnormal values Values greater than 40 are suggestive of Hurler’s syndrome. Cost $15–$50 for the screening test. Comments Improper specimen collection or handling will interfere with interpretation of results. Heparin therapy can cause elevated levels. False-positive levels occur in 5% of urine screening tests for acid mucopolysaccharides. acid phosphatase Any of a group of enzymes present in the prostate, semen, liver, spleen, red blood cells, bone marrow, and platelets that can be separated and analyzed according to their source. Serum levels of acid phosphatase were formerly measured to diagnose and monitor the progression of prostate cancer. However, serum levels of PSA (prostatic specific antigen) are more specific and now represent the method of choice. Patient preparation Any manipulation of the prostate, such as massage, catheterization, or rectal examination should not be performed within 48 hours of obtaining the specimen. Procedure The procedure consists of measuring the acid phosphatase in the serum by various laboratory methods.
acquired immunodeficiency syndrome
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5
Specimen Serum. When performed outside the hospital setting, the serum
must be separated from the red blood cells and frozen before sending it to the laboratory. Reference range Less than 3.0 mg/L. Abnormal values
Increased in: prostate carcinoma, prostate infarction, Paget’s disease of bone, Gaucher’s disease, multiple myeloma. Cost $15–$45. Comments This test is not specific for prostate cancer; prostate manipulation and hemolysis cause falsely elevated results. Acid phosphatase levels drop abruptly if the specimen is not properly preserved. See prostatespecific antigen. acquired immunodeficiency syndrome (AIDS) This disease has been linked with the human immunodeficiency virus (HIV), which invades specific cells of the immune system. This causes a decline in the body’s ability to fight infection, resulting in secondary infections by microorganisms that do not normally cause disease. HIV infection may be present for as long as 10 years before the symptoms of AIDS appear. Testing for HIV is strictly regulated by state and federal agencies because of the well-known social impact of HIV positivity. Information about HIV test results are confidential and may only be sent to nonphysicians with the written consent of the patient. Several types of tests have been used to detect and monitor HIV infection, including direct tests that measure the number of viral particles and indirect tests that measure the body’s reaction to the virus. OraSure is available through physicians and uses a sponge to obtain mucosal secretions from the mouth. Screening tests These tests are known by the acronym ELISA (enzymelinked immunosorbent assay) and detect antibodies to HIV that may be present in the patient’s blood. Screening tests are used by blood banks to detect HIV-infected blood, which if transfused, virtually guarantees that the recipient will become infected with HIV. Screening tests generally detect the HIV antibodies approximately four to eight weeks after infection. HIV is evaluated directly by the viral load test, which measures the virus’s ribonucleic acid (RNA). All positive screening tests are then retested by Western blot technique, which while more specific than the ELISA procedures, is more costly and difficult to perform. Monitoring tests These tests monitor the course of AIDS and response to treatment. T cells or T lymphocytes are quantified in the serum to assess the patient’s immune status. In general, the lower the number of T cells, the poorer the response to infections. T cells are a type of white blood cell and a key component of the immune response. The most commonly performed monitoring test for AIDS is measurement of a subset of T cells known as CD4 (“helper”) T cells, which help other immune cells function in an optimal fashion and, in the healthy individual, are more abundant than another set of T cells known as CD8 cells. As AIDS progresses, the number of all
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ACTH
T cells decreases, especially the CD4 T cells. The number of B cells, the other major type of lymphocyte responsible for producing antibodies, usually remains normal throughout the course of AIDS. Another standard means of monitoring AIDS is by the viral load test, which measures the number of copies of HIV RNA based on the polymerase chain reaction (PCR). Patient preparation No preparation is required, other than for drawing blood. Procedure ELISA is performed on serum. T cell analysis and viral load testing require whole blood specimens which are obtained within 24 hours of testing. Specimen Serum for ELISA. Heparanized whole blood for T cell and viral load studies, which must be kept at room temperature before testing. Reference range
ELISA Negative. PCR Negative. CD4:CD8 ratio Greater than 1. CD4 T cells Greater than 2,000. Western blot Negative. HIV RNA Quantitation Negative. Abnormal values Positive findings in any of the above tests when confirmed by Western blot are diagnostic of HIV infection. Cost
ELISA $25–$50. PCR $25–$150. CD4:CD8 ratio $65–$150. CD4 T cells $75–$150. Western blot $30–$75. HIV RNA Quantitation $200–$300. Comments False-positive (i.e., reporting a person as positive for HIV who is actually negative) results for HIV testing are extremely unusual given the use of confirmatory tests, particularly the Western blot. False-negative (i.e., reporting a person as negative for HIV who is actually positive) results for HIV can occur during the “window period” (i.e., between the time a person is infected with HIV and the time enough HIV antibodies are produced to be detected by the ELISA test). ACTH See adrenocorticotropic hormone. activated partial thromboplastin time See partial thromboplastin time. acute phase reactants (APR) Acute phase reactants are proteins that rise and fall with acute inflammation. These proteins migrate in specific regions of a slab of gelatin-like material that has been subjected to an electric current. These proteins include alpha -antitrypsin, alpha1-acid glycoprotein, amyloid A and P, anti-thrombin III, C-reactive protein, C1-esterase inhibitor, C3 complement, ceruloplasmin, fibrinogen, haptoglobin, orosomu1
adenovirus
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7
coid, plasminogen, and transferrin. Screening tests for acute phase reaction are nonspecific and include erythrocyte sedimentation rate (ESR), plasma viscosity, and zeta sedimentation rate. Patient preparation No preparation is required. Procedure The serum is analyzed by placing it on a special tube and measuring how quickly the red blood cells settle to the bottom, which is known as the erythrocyte sedimentation rate. Specimen Whole blood. Reference range The normal ESR is 0 to 20 millimeters/hour. Abnormal values
Increased in: pregnancy, acute and chronic inflammation, tuberculosis paraproteinemias (e.g., Waldenström’s macroglobulinemia), rheumatoid arthritis. Decreased in: polycythemia, sickle-cell anemia, hyperviscosity, low fibrinogen. Comments The normal range of acute phase reactants increases with age, while the absolute rates of speed at which the blood settles decrease. adenovirus Any of a family of viruses that cause noninfluenzal acute respiratory disease, pneumonia, epidemic keratoconjunctivitis, acute febrile pharyngitis, and acute hemorrhagic cystitis. The tests for adenovirus either measure antibodies to adenovirus or detect adenovirus antigens by immune (antigen-antibody) reactions. Both types of tests are known as serologic tests because they are performed on the serum. Adenoviruses can also be cultured, but because viral cultures are cumbersome and time-consuming, serologic methods are preferred by many laboratories. Asymptomatic infections (e.g., without flu symptoms) with adenoviruses are common and may make it difficult to interpret the serum levels of the immunoglobulin (antibody) response to infection. As a rule, immunoglobulin M (IgM), a specific antibody, increases when a person is first exposed to a particular microorganism. After the acute infection resolves, an immunoglobulin G (IgG) antibody to the virus is produced, which usually indicates protection against future infections by the causative virus. Patient preparation For the serologic tests, no preparation is required. There may be some discomfort associated with obtaining specimens from the throat or rectum. Procedure The serologic procedure consists of measuring the levels of the IgG and IgM antibodies in the serum. To culture a virus, the specimen must be inoculated on one of several cell types, since viruses cannot grow outside of living cells. After a period of several days, the cells are examined by a microscope to detect specific changes caused by adenoviruses. Specimen Serum for serologic diagnosis. Throat, rectal, and bladder specimens for culturing the virus. Reference range The normal values for adenovirus antibodies are somewhat patient-specific, as each person differs in his or her ability to produce antibodies. In absence of adenovirus, the culture cells have no changes.
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ADH
Abnormal values Patients infected with adenovirus usually demonstrate a
four-fold increase in titers from the “acute” serum and the “convalescent” serum. Infected cells in culture demonstrate typical changes seen by microscopy. Cost
Serology $15–$100. Viral culture $110–$150. ADH
See antidiuretic hormone.
adrenal antibodies A general term for antibodies that are formed against components of the adrenal gland. These antibodies occur in 40% to 60% of patients with adrenal insufficiency (Addison’s disease). Patient preparation No preparation is required. Procedure These antibodies are identified by covering a test tissue (e.g., monkey adrenal gland) with the patient’s serum. If adrenal antibodies are present, they can be detected by the technique of indirect immunofluorescence. Specimen Serum. Reference range None present. Abnormal values Adrenal antibodies are found in adrenal insufficiency (Addison’s disease), idiopathic hypoparathyroidism. Cost $18–$171. adrenocorticotropic hormone (ACTH, corticotropin) ACTH is a hormone secreted by the anterior pituitary gland that signals the adrenal gland to release steroids (cortisol, androgens, and aldosterone), critical to the normal functioning of the body. ACTH levels in the serum vary during the course of the day, peaking in the morning between 6 and 8 A.M. and in the evening between 6 and 11 P.M. ACTH is not routinely measured because it degrades in the plasma and is not required to diagnose routinely encountered clinical conditions. However, in patients with Cushing’s syndrome, ACTH measurement is extremely important because ACTH levels help determine where the lesion is located. Patient preparation The patient’s physical activity should be restricted for 10 to 12 hours before testing. Medications (particularly corticosteroids) that may interfere with ACTH testing should be withheld for 48 hours if possible. The patient should be placed on a low-carbohydrate diet for two days before testing. Procedure The serum is analyzed by immunoassay. Specimen Plasma, frozen within 15 minutes. For suspected adrenal hypofunction, the sample should be obtained from the patient between 6 and 8 A.M. To rule out Cushing’s syndrome as a diagnostic consideration, the venipuncture must be performed between 6 and 11 P.M. The sample should be collected in a plastic test tube or a heparinized tube, packed in ice, and sent to the laboratory immediately.
alanine aminotransferase
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Reference range ACTH levels less than 120 pg/ml. Abnormal values
Increased in: adrenal insufficiency (Addison’s disease), congenital adrenal hyperplasia, Cushing’s disease, ectopic ACTH-producing tumors, Nelson’s syndrome. Decreased in: secondary adrenocortical insufficiency, adrenal carcinoma, adenoma. Cost $50–$75. Comments Because of ACTH’s variability over the course of the day, its diagnostic significance and reliability are limited. Confirmation of increased or decreased ACTH levels may require ACTH suppression or stimulation testing to evaluate changes in the functional activity of the adrenal gland. aerobic culture See bacterial culture. AFP
See alpha-fetoprotein.
airway resistance Airway resistance is the resistance to the flow of air in the upper airways, which is evaluated in pulmonary function tests. It is the result of the natural recoil (resiliency) of the upper airway structures (the oral and nasal cavities, larynx, and the nonrespiratory portions of the lungs, including the trachea, bronchi, and bronchioles), through which the air passes on the way to the functional portion of the lungs, the alveoli. Airway resistance testing includes evaluation of airway responsiveness, provocation testing (e.g., bronchial challenge), evaluation of sites of airflow resistance or closures, and characterization of the type of lung disease. Patient preparation The patient should avoid heavy meals three hours before the test. This is a non-invasive test which measures the pressure of breathing under various conditions. Procedure Noseclips and a mouthpiece are placed on the patient, who is then seated inside a chamber known as a body plethysmograph. Once the chamber is sealed and the pressure reaches an equilibrium, the patient is told to pant lightly, which reflects the resistance to airflow. Reference range 0.6–2.8 cm H2O/liters per second. Abnormal values
Increased in: asthma, chronic obstructive lung disease, smokers. Cost $100–$200.
ALA See delta-aminolevulinic acid. alanine aminotransferase (ALT, serum glutamine pyruvic transaminase, SGPT) Alanine aminotransferase is an enzyme found primarily in the liver, with lesser amounts present in the kidneys, heart, and muscles. Under normal conditions, the levels of ALT in the blood are low. When liver damage occurs, ALT is released into the bloodstream, usually before the more obvious clinical findings (e.g., jaundice) of liver damage occur. ALT levels are
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albumin
useful as an early indicator of liver damage. The analysis of this enzyme is often included as part of a panel of blood chemistry tests. Specimen Serum or heparinized plasma. Reference range
Men Women Children
10–32 units/L. 9–24 units/L. 2 times that of adults.
Abnormal values
Increased in: viral or drug-induced hepatitis, infectious mononucleosis, chronic hepatitis, intrahepatic cholestasis, cholecystitis, active cirrhosis, acute myocardial infarction. Cost $10–$20 when performed as a single test. Comments The measurement of ALT alone has little diagnostic value and must be combined with other chemistry assays and clinical indicators. albumin The most abundant protein in blood circulation, albumin is needed to maintain the osmotic pressure within blood vessels, without which fluids would leak out of the circulation. Albumin provides nutrition to tissues and binds to various molecules, such as hormones, vitamins, drugs, and enzymes, transporting them through the body. Albumin is synthesized in the liver and is extremely sensitive to liver damage. Hypoalbuminemia, the decrease in albumin, may be caused by liver damage, inadequate dietary intake of protein as occurs in malnutrition, and renal disease, in which albumin and other proteins are not retained by the kidneys. Dehydration causes an increase in albumin concentration, known as hyperalbuminemia. Patient preparation Urine measurements require a 24-hour collection period. See timed collection. Procedure Analysis of albumin is generally done as part of a chemistry profile on an automated analyzer. Specimen Albumin can be measured in serum, cerebrospinal fluid, and urine. Serum measurements of albumin are usually part of a multichannel chemical analysis of the blood, while albumin in cerebrospinal fluid and urine is measured singly. Reference range
Serum, male Serum, female Urine Cerebrospinal fluid
4.2–5.5 g/dL. 3.7–5.3 g/dL. 3.9–24.4 mg/24 hrs. 15–45 mg/dL.
Abnormal values
Increased in: dehydration. Decreased in: liver disease, chronic disease, neoplasia, thyroid disease, burns, heart failure. Cost $8–$35 when performed as a single test. Comments Decreased albumin in serum suggests liver disease. The “liver enzymes” (alanine aminotransferase and aspartate aminotransferase) must be evaluated in conjunction with albumin to confirm the presence of
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liver damage. The presence of albumin in urine generally signifies kidney disease. alcohol The alcohol consumed in alcoholic beverages such as beer, wine, and liquors is ethyl alcohol (ethanol). After ethanol is consumed, it reaches a peak in the blood in about 30 minutes. Approximately three hours are needed to metabolize and eliminate each ounce of ethanol ingested. Blood alcohol measurements are fairly reliable for many hours after a person ingests the last drink. Patient preparation No preparation is required. When blood samples are used, the venipuncture site must not be cleaned with alcohol pads because this would contaminate the specimen. The urine collection need not be a timed specimen. Procedure Breath measurements are generally carried out by law enforcement officers, often at the site of a traffic violation where alcohol use is suspected. Alcohols are volatile substances; therefore it is important that the specimen container be kept tightly sealed until the time of analysis. Serum and urine ethanol are measured in the laboratory by immunoassay or gas-liquid chromatography; other alcohols are measured by gas-liquid chromatograpy. Specimen Ethanol can be measured in the blood, breath, or urine. Reference range Negative. Greater than 0.05% (50 mg/dL) may impair judgment. Abnormal values Elevated levels of alcohol cause inebriation, and liver and brain damage. Cost $25–$75. The test is more expensive when used for legal purposes. Comments Blood is more accurate than urine for quantifying alcohol. Proper specimen handling is extremely important for accurate results. aldolase Aldolase is an enzyme that converts sugar to energy. Though most prominent in skeletal muscle, it is present in all tissues. Aldolase is elevated in the serum in skeletal muscle disease or injury and is less common in other conditions. It is measured when inflammatory disease of muscle (myopathy) is suspected. The intensity of the increase reflects the severity of the myopathy, and it can be measured serially to monitor the effect of corticosteroid therapy on the course of disease. Aldolase may also be elevated early in the clinical course of patients with muscular dystrophy. Patient preparation Patient should fast for eight hours before the test. Procedure Aldolase is determined by the conversion of an uncolored substance to a colored substance that is measured by spectrophotometry. Specimen Serum should be separated and frozen as quickly as possible. Reference range 3.1–7.5 units/L. Abnormal values
Increased in: Duchenne’s muscular dystrophy, dermatomyositis, polymyositis, trichinosis, metastatic carcinoma, myelocytic leukemia, megaloblastic anemia, hemolytic anemia, tissue death (infarction). Cost $15–$60.
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aldosterone
Comments Aldolase is not commonly requested by physicians unless they are monitoring muscle diseases.
aldosterone Aldosterone is a hormone of the adrenal gland that helps control the electrolyte balance in the body by regulating the reabsorption of sodium and chloride in exchange for potassium and hydrogen ions in the kidneys. Aldosterone helps maintain blood pressure and blood volume. Secretion of aldosterone is controlled by the renin-angiotensin system, which produces an enzyme, angiotensin II, that stimulates the synthesis and secretion of aldosterone. Secretion of aldosterone is also controlled by concentrations of potassium in the circulation. High serum potassium levels elicit secretion of aldosterone, while low concentrations of sodium cause the release of renin which stimulates aldosterone secretion. Aldosterone measurements are used increasingly in the study of hypertension. Patient preparation The patient should be on a normal salt diet. Diuretics, antihypertensive drugs, oral contraceptives, estrogens, and licorice (which can cause hypertension) should be terminated two to four hours before testing. No recent radionuclide studies (scans) should be performed before drawing the specimen. Procedure The patient must be at rest and lying down for the first venipuncture. Postural changes are evaluated by drawing another sample while the patient is up and about four hours after the initial specimen is collected. Aldosterone can also be measured in 24-hour urine samples. Measurements are made by RIA methods. Specimen Serum, plasma, or urine. Specimens should be transported on ice and frozen as soon as possible after being obtained. Reference range Plasma levels are less than 20 ng/dL in men, 30 ng/dL in non-pregnant women, 100 ng/dL in pregnant women, and 70 ng/dL in children. Urine levels are usually less than 50 µg/24 hours. Abnormal values
Increased in: adrenocortical adenoma or carcinoma, bilateral adrenal hyperplasia, renovascular hypertension, liver disease, congestive heart failure, cirrhosis, nephrotic syndrome, pregnancy 3rd trimester). Decreased in: primary hypoaldosteronism, salt losing syndrome, toxemia of pregnancy. Cost $60–$175. Comments Failure to observe dietary restrictions or postural procedures interferes with the interpretation of test results. Aldosterone is generally measured with potassium, sodium, and renin levels in evaluating hypertension and suspected lesions of the adrenal gland. alkaline phosphatase (ALP, alk phos) Alkaline phosphatase (ALP) is an enzyme normally present in the blood. Various subtypes known as isoenzymes are found in the liver, intestine, and bone cells. ALP is involved in bone calcification, and lipid and metabolite transportation. Conditions that stimulate bone cell activity cause elevated levels of alkaline phosphatase. The liver isoenzyme of ALP is elevated in biliary obstruction. Because an elevated
alkaline phosphatase isoenzymes
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total ALP level can indicate either liver or bone disease, additional studies must be carried out to determine the exact cause of the elevation. Since ALP concentrations rise during active bone formation in growth, infants, children, and adolescents normally have levels up to three times those of adults. Pregnancy can also cause an increase in ALP levels. Patient preparation No preparation is required. Procedure Alkaline phosphatase is measured by spectrophometry. Specimen Serum. Reference range Because reference ranges are dependent on the methodology used by the laboratory, these ranges can vary widely. In adult males, the range is 90–250 units/liter; in adult females, 80–200 units/liter. Abnormal values
Increased in: hepatobiliary disease (e.g., viral hepatitis), severe biliary obstruction, biliary cirrhosis, intrahepatic cholestasis, Paget’s disease of bone, osteomalacia, osteogenic sarcoma, bone metastasis, hyperparathyroidism, infectious mononucleosis. Decreased in: hypophosphatasia, protein deficiency, magnesium deficiency. Cost $10–$40 when performed as a single test. Comments Because ALP exists in various tissues, the finding of elevated levels of total ALP must be followed by more specific testing such as ALP isoenzymes. Additional studies of bone or liver chemistries are used to determine the primary cause of elevations. ALP is generally part of a routine chemistry profile. alkaline phosphatase isoenzymes Alkaline phosphatase is an enzyme with several subtypes known as isoenzymes, which are more common in certain organs. The isoenzymes of greatest clinical significance are those that occur in the liver, bone, intestine, and placenta. The intestinal isoenzyme occurs almost exclusively in individuals with blood group B or O and is markedly elevated eight hours after a fatty meal. The placental isoenzyme first appears in mid to late pregnancy, accounts for half of all alkaline phosphatase during the third trimester, and drops to normal levels after the woman delivers. Another, the Regan isoenzyme, resembles the placental isoenzyme of alkaline phosphatase and is present in some patients with cancer. A number of methods have been developed in the laboratory to separate the isoenzymes according to subtype. The primary use of this test is to determine which type of ALP isoenzyme is predominant when there is an elevation in total alkaline phosphatase. Patient preparation No preparation is required. Procedure ALP isoenzymes can be measured by a variety of methods. The older methods involve heating or treating with urea. Currently, electrophoresis or isoelectric focusing are the methods of choice. Specimen Serum. Reference range
Liver Bone
20–130 units/L. 20–120 units/L.
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allergy testing
Abnormal values An increase in the bone ALP isoenzymes usually indicates
Paget’s disease of the bone. Bone isoenzymes are also increased in boneforming tumors and in pregnancy. Cost $10–$80. Comments This test should not be performed if the total alkaline phosphatase levels are within the laboratory’s reference (i.e., normal) range, because the results would have little clinical significance. These tests are only semiquantitative and are subject to significant variation. Other laboratory tests and clinical findings should be used in conjunction with alkaline phosphatase isoenzymes when making a diagnosis. allergy testing
See RAST.
alpha1-antitrypsin (A1AT) Alpha1-antitrypsin is a protein that inhibits proteolytic enzymes (enzymes that break down proteins). Enzymes that are broken down by A1AT include trypsin, chymotrypsin, elastase, plasmin, thrombin, and others. The normal A1AT serum levels of 2–4 g/L rise nonspecifically during inflammation and are usually increased in acute inflammation, severe infection, and necrosis. The A1AT gene has 25 different forms which are classified by how they respond to electrophoresis. The PiMM type of A1AT is normal. The most common form seen in A1AT deficiency is designated PiZZ, which is characterized by early-onset emphysema and cholestasis, cirrhosis, hepatic failure, and a markedly increased risk of liver cancer. Patient preparation The patient should not eat for several hours before drawing the specimen Procedure A1AT is measured by nephelometry. Specimen Serum. Reference range 78–200 mg/dL. Abnormal values
Increased in: inflammatory disorders, malignancies, hormonal effects, brain infarction, systemic lupus erythematosus, Hashimoto’s thyroiditis. Decreased in: nephrotic syndrome, protein-losing gastroenteropathies, prematurity, acute hepatitis, respiratory distress syndrome, acute pancreatitis, congenital defects, emphysema. Cost $20–$80. Comments This test can be a useful indicator in patients at risk for emphysema. alpha-fetoprotein (AFP) Alpha-fetoprotein is a glycoprotein produced by the fetal liver. The peak production occurs at 13 weeks of age, after which the production progressively declines. AFP is detected in pregnancy in both the mother’s serum and in the amniotic fluid. The AFP levels are greater in twins and in “higher multiple” pregnancies, and its measurement is now a part of routine pregnancy testing. If the fetal neural tube, which develops into the brain and spinal cord, fails to close completely, large quantities of
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AFP enter the amniotic fluid, resulting in elevated levels in the mother’s serum. Neural tube defects associated with increased AFP include spina bifida, anencephaly myelocele, and hydrocephalus. AFP is also elevated in certain malformations, including congenital nephrosis, esophageal atresia, duodenal atresia, and fetal bleeding into the amniotic cavity. AFP levels are usually measured at 13–16 weeks of pregnancy, when the fetal AFP production is highest. Confirmatory tests such as amniocentesis and/or ultrasonography are used to identify neural tube defects when elevated AFP levels are identified. If these tests suggest the presence of significant birth defects, the woman may choose to terminate the pregnancy. After birth, elevated serum AFP levels occur only in conditions of abnormal cell multiplication. Although AFP measurement is not approved by the U.S. Food and Drug Administration for cancer screening, it is regularly used to detect and monitor therapy of liver cancer (hepatocellular carcinoma) and certain tumors of the gonads (testes and ovaries), retroperitoneum, and mediastinum. Patient preparation No preparation is required. Procedure AFP is measured by ELISA, FPIA, or chemiluminescent methods. Specimen Serum or amniotic fluid; when the mother’s serum is screened for the presence of AFP, the serum should be drawn between weeks 13–16 of pregnancy. Reference range
Nonpregnant adults Maternal serum (13–16 wks) Amniotic fluid (13–16 wks)